The overall program is designed to elucidate the pathogenesis of diabetes mellitus. Emphasis is placed on the demonstrated failure of the B cells of the islets to respond appropriately to glucose as a stimulator of insulin release. Investigation is focused upon cAMP in isolated rat islets and the control of its concentration and subcellular distribution. The role of glucose and other secretagogues on the above will be determined. It is anticipated that compartmentalization of cAMP may exist and that this may explain the dissociation between cAMP levels and insulin release with various insulin secretagogues. BIBLIOGRAPHIC REFERENCE: Lavine, R.L., Voyles, N., Perrino, P. and Recant, L. The effect of fasting on tissue cAMP and plasma glucagon in the obese hyperglycemic mouse. Endocrinology 97: September 1975.